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(Circulation Research. 2004;94:1630.)
© 2004 American Heart Association, Inc.

Clinical Research

Cardiac Angiotensin II Participates in Coronary Microvessel Inflammation of Unstable Angina and Strengthens the Immunomediated Component

Gian Gastone Neri Serneri, Maria Boddi, Pietro Amedeo Modesti, Mirella Coppo, Ilaria Cecioni, Thomas Toscano, Maria Letizia Papa, Manuela Bandinelli, Gian Franco Lisi, Mario Chiavarelli

From the Clinica Medica Generale e Cardiologia (G.G.N., M.B., P.A.M., I.C., M.C., M.L.P., M.B., G.F.L.), University of Florence, Italy; and Institute of Thoracic and Cardiovascular Surgery (T.T., M.C.), University of Siena, Italy.

Correspondence to Dr Gian Gastone Neri Serneri, Clinica Medica Generale e Cardiologia, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. E-mail gg.neriserneri{at}dfc.unifi.it

Angiotensin (Ang) II is now recognized to be a mediator of a wide variety of inflammatory processes. This study investigated renin-angiotensin system (RAS) components and a number of inflammatory mediators in left ventricular biopsies from 2-vessel disease unstable angina (UA) (n=43) and stable angina (SA) (n=15) patients undergoing coronary bypass surgery. Biopsy samples from 6 patients undergoing valve replacement for mitral stenosis served as controls. UA patients were randomly assigned to angiotensin-converting enzyme (ACE)-inhibitor (ramipril), AT1 antagonist (valsartan), or placebo and treated during the 5 days preceding coronary bypass surgery, performed from 6 to 9 days after coronary angiography. During coronary angiography coronary blood flow was measured and samples were obtained from aorta and coronary sinus for determination of Ang I and Ang II gradients. The hearts of UA patients produced Ang II in a greater amount than in SA patients (P<0.01). UA biopsy samples showed numerous DR⁺ cells, identified as lymphocytes, macrophages, and endothelial cells. Reverse-transcriptase polymerase chain reaction showed overexpression of AGTN, ACE, and AT1-R genes, as well as upregulation of TNF-, IL-6, IFN-, and iNOS genes (P<0.01), with no differences between nonischemic and potentially ischemic areas. AGTN, ACE, and cytokine genes were mainly localized on endothelial cells. Ramipril and valsartan markedly decreased the expression levels of TNF-, IL-6, and iNOS, and, to a lesser extent, of IFN- genes, but did not affect the number of DR⁺ cells, with no significant difference between the 2 treatments. These results show that locally generated Ang II amplifies the immunomediated inflammatory process of coronary microvessels occurring in unstable angina.

Key Words: angiotensin II • unstable angina • myocardial inflammation

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